Asymmetric total syntheses of (+)-mycoepoxydiene and related natural product (-)-1893A: application of one-pot ring-opening/cross/ring-closing metathesis to construct their 9-oxabicyclo[4.2.1]nona-2,4-diene skeleton

The total syntheses of (+)-mycoepoxydiene and (-)-1893A have been completed. The present synthetic strategy features the use of one-pot ring-opening/cross metathesis (ROM/CM) followed by a ring-closing metathesis (RCM) reaction, allowing for the concise construction of the 9-oxabicyclo[4.2.1]nona-2,4-diene framework from a 7-oxabicyclo[2.2.1]hept-2-ene derivative and 1,3-butadiene. The sequential metathesis product was converted into (+)-mycoepoxydiene through the oxidative rearrangement of a furfuryl alcohol to a pyranone, thereby establishing its absolute stereochemistry. From the common intermediate, a structurally related natural product (-)-1893A was also synthesized via the vinylogous aldol reaction.     

Absolute stereochemistries and total synthesis of (+)-arisugacins A and B, potent, orally bioactive and selective inhibitors of acetylcholinesterase

In the current studies, we used the Kakisawa-Kashman modification of the Mosher NMR method to determine the complete absolute stereochemistry of arisugacins. We also report the convergent total synthesis of (+)-arisugacins A and B by a sequence including (i) ruthenium complex-catalyzed asymmetric reduction of the cyclohexenone derivative; (ii) stereoselective construction of the arisugacin skeleton by a Knoevenagel-type reaction of an α,β-unsaturated aldehyde derivative with production of a 4-hydroxy-2-pyrone derivative as a key reaction; and (iii) stereoselective dihydroxylation to give the diol derivative, followed by deoxygenation. Accordingly, we defined the absolute structures of arisugacins A and B as 4a-(R),6a-(R),12a-(R), and 12b-(S). Finally, we characterized the bioactivities of the synthetic intermediates to understand the structure-activity relationships of the arisugacins.     

Perturbation analysis for the rotational spectrum of the NiBr radical in the X2Pi3/2 and A2Delta5/2 states

The millimeter- and submillimeter-wave spectra of the NiBr radical in the X (2)Pi(3/2) and A (2)Delta(5/2) states were observed by a source-modulated microwave spectrometer. The NiBr radical was generated in a dc glow discharge through the mixture of Br(2) vapor and Ar gas by the sputtering reaction with a Ni cathode. Observed transition frequencies were independently analyzed for both electronic states using a standard polynomial expression of a Hund's case (c) approximation. Anomalous behavior of the effective molecular constants in the X (2)Pi(3/2) state was interpreted as the result of the perturbation between the X (2)Pi(3/2) and A (2)Delta(5/2) states. The deperturbed molecular constants were derived using a simplified supermultiplet Hamiltonian including the interaction terms between the two electronic states.     

Site-directed 13C solid-state NMR studies on membrane proteins: strategy and goals toward revealing conformation and dynamics as illustrated for bacteriorhodopsin labeled with [1-13C]amino acid residues

We have so far demonstrated that well-resolved and site-specifically assigned (13)C peaks as recorded by site-directed NMR study on (13)C-labeled membrane proteins can serve as a convenient probe to reveal their local conformation and dynamics. We attempted here to clarify the extent to which (13)C NMR spectra of (13)C-labeled fully hydrated bacteriorhodopsin (bR) as a typical membrane protein are visible or well resolved in the presence of inherent fluctuation motions with frequency of 10(2)-10(8) Hz, especially at the membrane surfaces. Accordingly, we estimated the relative proportion of (13)C NMR signals from the surface areas with and without peak suppression by the accelerated transverse relaxation effect by surface-bound Mn(2+) ions, which could be effective for residues within 8.7 angstroms of the membrane surface. It turned out that the experimental findings are consistent with the predicted amount of amino acid residues under consideration located within 8.7 angstroms of the surface for [1-(13)C]Val- and Ile-labeled bR and also [3-(13)C]Ala-bR. In contrast, (13)C NMR peaks from such surfaces area are almost completely or partially suppressed for [1-(13)C]Gly-, Ala-, Leu-, Phe- and Trp-labeled bR, as a result of plausible interference of the fluctuation frequency with frequency of magic angle spinning (10(4) Hz). We further assigned several (13)C NMR signals of [1-(13)C] Val-, Trp- and Ile-labeled bR on the basis of a variety of site-directed mutants with reference to those of the wild type. Further, we recorded the (13)C NMR of bR in lipid bilayers to search for the optimal conditions to be able to obtain signals with the highest peak intensities and spectral resolution. Backbone dynamics turn out to be essential for recording (13)C NMR spectra so as to escape from motional frequencies of the order of 10(4)-10(5) Hz, either in the direction of accelerated fluctuation or slowed motions in the direction of forming the 2D array.     

The effects of epimerization at the 3(1)-position of bacteriochlorophylls c on their aggregation in chlorosomes of green sulfur bacteria. Control of the ratio of 3(1) epimers by light intensity

R- and S-epimerization at the 3(1) position of bacteriochlorophyll (BChl) c and the formation of rod-like aggregates in chlorosomes of green sulfur bacteria were markedly affected in Chlorobium (Cb.) tepidum and Cb. limicola by cultivation under various light intensities (photon fluence rate). The stronger the light, the higher the ratio of the S-epimer to the R-epimer for each homolog of BChl c in the bacteria. S[P,E] BChl cF and S[I,E] BChl cF were found to be the major S-epimers in Cb. tepidum and Cb. limicola, respectively. R[P,E] BChl cF decreased markedly compared to R[E,E] BChl cF in Cb. tepidum, whereas no observable change in the ratio of R[P,E]/R[E,E] was detected for Cb. limicola. With increase in light intensity the Qy absorption maximum of the bacteria shifted to shorter wavelengths. In vitro spectroscopic studies of the aggregates showed a marked difference in the formation of aggregates from R- and S-epimers of BChl c; the S-epimers formed aggregates much more slowly than did the R-epimers. These results suggest that the ratio of the epimers of BChl c might significantly affect the aggregation of BChl in the chlorosome. We propose different roles for the R- and S-epimers in chlorosomes of Cb. limicola and Cb. tepidum.     

A novel boron-rich quaternary scandium borocarbosilicide Sc3.67−xB41.4−y−zC0.67+zSi0.33−w

A novel quaternary scandium borocarbosilicide Sc_3.67−xB_41.4−y−zC_0.67+zSi_0.33−w was found. Single crystallites were obtained as an intergrowth phase in the float-zoned single crystal of Sc_0.83−xB_10.0−yC_0.17+ySi_0.083−z that has a face-centered cubic crystal structure. Single crystal structure analysis revealed that the compound has a hexagonal structure with lattice constants a = b = 1.43055(8) nm and c = 2.37477(13) nm and space group (No. 187). The crystal composition calculated from the structure analysis for the crystal with x = 0.52, y = 1.42, z = 1.17, and w = 0.02 was ScB_12.3C_0.58Si_0.10 and that agreed rather well with the composition of ScB_11.5C_0.61Si_0.04 measured by EPMA. In the crystal structure that is a new structure type of boron-rich borides, there are 79 structurally independent atomic sites, 69 boron and/or carbon sites, two silicon sites and eight scandium sites. Boron and carbon form seven structurally independent B₁₂ icosahedra, one B₉ polyhedron, one B₁₀ polyhedron, one irregularly shaped B₁₆ polyhedron in which only 10.7 boron atoms are available because of partial occupancies and 10 bridging sites. All polyhedron units and bridging site atoms interconnect each other forming a three-dimensional boron framework structure. Sc atoms reside in the open spaces in the boron framework structure.     

Lewis acid-activated chiral leaving group: enantioselective electrophilic addition to prochiral olefins

A new strategy using a BINOL derivative as a chiral leaving group and Lewis acid has been developed for enantioselective alkylation of prochiral olefins. (R)-2,2'-Bis[2-(trimethylsilyl)ethoxymethyl]-1,1'-binaphthol is demonstrated to be an effective reagent for enantioselective hydroxymethylation of silyl enol ethers and trisubstituted alkenes. Electrophilic addition to prochiral olefins is accompanied by cleavage of an acetal that is dual activated by SnCl4 and the delta-effect of silicon through the S(N)2 substitution process. Enantioselective synthesis of cyclic terpenes is also described using this strategy.     

Chiral self-dimerization of vanadium complexes on a SiO2 surface: the first heterogeneous catalyst for asymmetric 2-naphthol coupling

The self-dimerized chiral assembly of vanadium-Schiff-base complexes was found to occur on a SiO2 surface and to be the first heterogeneous catalyst for the asymmetric oxidative coupling of 2-naphthol with 100% selectivity and 90% enantioselectivity.     

Structural analysis of amylose tris(3,5-dimethylphenylcarbamate) by NMR relevant to its chiral recognition mechanism in HPLC

The structural analysis of amylose tris(3,5-dimethylphenylcarbamate) (ADMPC) was performed by NMR spectroscopy using a sample with a lower degree of polymerization in order to understand the chiral recognition mechanism when it was used as a chiral stationary phase (CSP) in high-performance liquid chromatography (HPLC). ADMPC exhibited chiral discrimination for many enantiomers, including 1-(9-anthryl)-2,2,2-trifluoroethanol (1) and 1,1'-bi-2-naphthol (2) in both NMR and HPLC. A good agreement was observed between the HPLC and NMR results when chloroform was employed as the common solvent. The structure of ADMPC in solution was investigated by NMR using the 2D NOESY technique coupled with computer modeling, and a left-handed 4/3 helical structure was obtained as the most probable one. The binding geometry between ADMPC and the enantiomers of 1 was also investigated by (1)H NMR titration. On the basis of these results combined with molecular modeling, a rational model to explain the chiral discrimination mechanism of 1 on ADMPC was proposed.     

Aryloxyacetic acid diuretics with uricosuric activity. II. Substituted [(4-oxo-4H-1-benzopyran-7-yl)oxy]acetic acids and the related compounds.

Di- and tri-substituted [(4-oxo-4H-1-benzopyran-7-yl)oxy]acetic acids, and 4-oxo-3-phenyl-4H-furo[2,3-h]-[1]benzopyran-8-carboxylic acid were synthesized and tested for natriuretic and uricosuric activities. Among the compounds tested, 3,5-disubstituted [(4-oxo-4H-1-benzopyran-7-yl)oxy]acetic acids (6c-f, h, n and x) showed potent natriuretic and uricosuric activities, whereas 4-oxo-3-phenyl-4H-furo[2,3-h][1]benzopyran-8-carboxylic acid (6dd) possessed only potent natriuretic activity. The structure-activity relationships are also discussed.